Smith M K, George E L, Zenick H, Manson J M, Stober J A
Health Effects Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, OH 45268.
Toxicology. 1987 Oct 12;46(1):83-93. doi: 10.1016/0300-483x(87)90140-5.
The developmental toxicity of acetonitrile and 5 halogenated derivatives was examined with an in vivo teratology screen adapted for use in the Long-Evans rat. The screen was extended to an evaluation of growth till postnatal Days 41-42, and weight of several organs at sacrifice. Acetonitrile was without developmental effects even at doses toxic to the dam. Of the halogenated compounds, treatment with trichloroacetonitrile (TCAN) and dichloroacetonitrile (DCAN) resulted in reduced fertility and increased early implantation failure. There was no effect on litter size in females bearing live litters, but pup birth weight was reduced in all litters exposed to halogenated compounds. Perinatal survival of the pups was adversely impacted by DCAN and TCAN. Postnatal growth till Day 4 was reduced by DCAN and bromochloroacetonitrile (BCAN) while growth till Day 42 was consistently affected only by TCAN. Some general observations were made on the usefulness of the criteria used in the screen, and TCAN, the most toxic of the halogenated compounds, was selected for further in-depth evaluation.
采用适用于长 Evans 大鼠的体内致畸学筛选方法,研究了乙腈及其 5 种卤代衍生物的发育毒性。该筛选方法扩展至对出生后 41 - 42 天生长情况以及处死时多个器官重量的评估。即便给予对母鼠有毒性的剂量,乙腈也未产生发育毒性效应。在卤代化合物中,用三氯乙腈(TCAN)和二氯乙腈(DCAN)处理会导致生育力下降以及早期着床失败增加。对于怀有活仔的雌性动物,窝仔数没有影响,但所有暴露于卤代化合物的窝仔中幼仔出生体重均降低。DCAN 和 TCAN 对幼仔围产期存活率产生不利影响。DCAN 和溴氯乙腈(BCAN)使出生后至第 4 天的生长减缓,而直至第 42 天的生长仅持续受到 TCAN 的影响。对筛选中使用的标准的实用性进行了一些一般性观察,并选择了毒性最大的卤代化合物 TCAN 进行进一步深入评估。